One of the first lines of host defense against many viruses in vertebrates is the innate immune system, which detects pathogen associated molecular patterns (PAMPs) using pathogen recognition receptors (PRR). The dynamic interactions between pathogens and hosts create, in some cases, species-specific relationships. Recently, it was shown that murine factor X (mFX)-armored human adenovirus (HAd) stimulated a mFX-Toll-like receptor 4 (TLR4)-associated response in mouse macrophages in vitro and in vivo. Given the importance of studies using animal to better understand host-pathogen interactions, we asked if a human FX (hFX)-armored HAd type 5 (HAd5) was capable of activating innate immune sensors in primary human mononuclear phagocytes. To this end we assayed human mononuclear phagocytes for their ability to be stimulated by hFX-armored HAd5 via a TLR/NF-kappa, and in particular a TLR4, pathway. In our hands, we found no significant interaction, activation, or maturation of human mononuclear phagocytes by hFX-armored HAd5. IMPORTANCE: Animals, and in particular mice, are often informative and powerful surrogates for how pathogens interact with natural host systems. When possible extended and targeted studies in the natural host can then be performed. Our data will help us understand the differences in preclinical testing in mice and clinical use in human in order to improve treatment for HAd diseases and Ad vector effectiveness.
Human coagulation factor X-adenovirus type 5 complexes poorly stimulate an innate immune response in human mononuclear phagocytes
Eichholz, K.; Mennechet, F.; Kremer, E. J.
2014-12-24 / vol Dec 24
JVI.03576-14 [pii] 10.1128/JVI.03576-14
1098-5514 (Electronic) 0022-538X (Linking)
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